TY - JOUR T1 - Vesicular storage and release of the novel sympathetic nerve tracer <sup>18</sup>F-LMI1195 JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 33 LP - 33 VL - 58 IS - supplement 1 AU - Rudolf Werner AU - Xinyu Chen AU - Constantin Lapa AU - Simon Robinson AU - Takahiro Higuchi Y1 - 2017/05/01 UR - http://jnm.snmjournals.org/content/58/supplement_1/33.abstract N2 - 33Objectives: Norepinephrine analogue tracer 18F-N-[3-bromo-4-(3-fluoro-propoxy)-benzyl]-guanidine (18F-LMI1195) is a new class of PET tracer designed for sympathetic nervous imaging of the heart. Although the favorable image quality with high and specific neural uptake are previously demonstrated in animals and humans, intracellular behavior is not yet fully understood. The aim of the present study was to verify whether 18F-LMI1195 was stored in storage vesicles and released in accompany with vesicle turnover.Methods: Two different kinds of norepinephrine transporter expressing cell lines were used for in vitro tracer uptake studies: PC12 (rat pheochromocytoma) and SK-N-SH (human neuroblastoma). After 2 h of 18F-LMI1195 loading into PC12 cells, effects of reserpine treatment (50 nM), as stimulant for storage vesicle turnover, were measured at 10, 20 and 30 min. As reference, 131I-MIBG uptake was also examined in the same manner.Results: Reserpine enhanced 18F-LMI1195 washout from PC12 cells, while tracer uptake remained stable in the SK-N-SH cells that lack catecholamine storage vesicles. 18F-LMI1195 washout rates from PC12 cells after 30min of reserpine treatment and control buffer were 53.0 ± 8.7 % and 20.8 ± 0.6 %, respectively. Similar tracer kinetics after reserpine treatments were confirmed with 131I-MIBG. 131I-MIBG washout rates from PC12 cells after 30min of reserpine treatment and control buffer were 65.3 ± 10.3 % and 26.7 ± 0.6 %, respectively.Conclusion: In vitro tracer uptake study confirmed both 18F-LMI1195 and 131I-MIBG are stored in vesicles after transported into cells, and released along with storage vesicle turnover. Understanding the basic kinetics of 18F-LMI1195 at subcellular level would help to design clinical imaging protocol and interpret imaging results. Research Support: This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement. This work was supported by the Competence Network of Heart Failure funded by the Integrated Research and Treatment Center (IFB) of the Federal Ministry of Education and Research (BMBF) and German Research Council (DFG grant HI 1789/2-1). $$graphic_BAC0C20D-B9C2-493A-8ACF-3E36A34CB0DA$$ ER -